A novel lens epithelium gene, LEP503, is highly conserved in different vertebrate species and is developmentally regulated in postnatal rat lens

The development of the lens is dependent on the proliferation of lens epith elial cells and their differentiation into fiber cells near the lens bow/eq uator. Identification of genes specifically expressed in the lens epithelia l cells and their functions may provide insight into molecular events that regulate the processes of lens epithelial cell differentiation. In this stu dy, a novel lens epithelium gene product. LEP503, identified from rat by a subtractive cDNA cloning strategy was investigated in the genome organizati on, mRNA expression and protein localization. The genomic sequences for LEP 503 isolated from rat, mouse and human span 1754 bp, 1694 bp and 1895 bp re gions encompassing the 5'-flanking region, two exons, one intron and 3'-fla nking region. All exon-intron junction sequences conform to the GT/AG rule, Both mouse and human LEP503 genes show very high identity (93% for mouse a nd 79% for human) to rat LEP503 gene in the exon 1 that contains an open re ading frame coding for a protein of 61 amino acid residues with a leucine-r ich domain. The deduced protein sequences also show high identity (91% betw een mouse and rat and 77% between human and rat). Western blot shows that L EP503 is present as a specific similar to 6.9 kDa band in the water-insolub le-urea-soluble fraction of lens cortex where lens epithelium is included. Immune-staining shows that LEP503 is localized in the epithelial cells alon g the entire anterior surface of rat lens. Developmentally, LEP503 is expre ssed at a low level at newborn, and then the expression level increases by about ten-fold around postnatal day 14 and remains at this high level for a bout 25 days before it drops back to the low level by postnatal day 84. The se data suggest that the LEP 503 may be an important lens epithelial cell g ene involving the processes of epithelial cell differentiation. (C) 2000 Ac ademic Press.